Contrasting proteome biology and functional heterogeneity of the 20 S proteasome complexes in mammalian tissues.
The 20 S proteasome complexes are major contributors to the intracellular protein degradation machinery in mammalian cells. Systematic administration of proteasome inhibitors to combat disease (e.g. cancer) has resulted in positive outcomes as well as adversary effects. The latter was attributed to, at least in part, a lack of understanding in the organ-specific responses to inhibitors and the potential diversity of proteomes of these complexes in different tissues. Accordingly, we conducted a proteomic study to characterize the 20 S proteasome complexes and their postulated organ-specific responses in the heart and liver. The cardiac and hepatic 20 S proteasomes were isolated from the same mouse strain with identical genetic background. We examined the molecular composition, complex assembly, post-translational modifications and associating partners of these proteasome complexes. Our results revealed an organ-specific molecular organization of the 20 S proteasomes with distinguished patterns of post-translational modifications as well as unique complex assembly characteristics. Furthermore, the proteome diversities are concomitant with a functional heterogeneity of the proteolytic patterns exhibited by these two organs. In particular, the heart and liver displayed distinct activity profiles to two proteasome inhibitors, epoxomicin and Z-Pro-Nle-Asp-H. Finally, the heart and liver demonstrated contrasting regulatory mechanisms from the associating partners of these proteasomes. The functional heterogeneity of the mammalian 20 S proteasome complexes underscores the concept of divergent proteomes among organs in the context of an identical genome.
Gomes
Aldrin V
AV
Department of Physiology and Medicine, Cardiac Proteomics and Signaling Laboratory at Cardiovascular Research Laboratory, University of California Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
Young
Glen W
GW
Wang
Yueju
Y
Zong
Chenggong
C
Eghbali
Mansoureh
M
Drews
Oliver
O
Lu
Haojie
H
Stefani
Enrico
E
Ping
Peipei
P
D000595:Amino Acid Sequence; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021122:Protein Subunits / Q000032:analysis / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification; D020543:Proteome / Q000378:metabolism*; D015203:Reproducibility of Results
D004791:Enzyme Inhibitors; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D020543:Proteome; D046988:Proteasome Endopeptidase Complex